In a number of mammalian systems, tumor rejection has been shown to be immunologically mediated. Rejection is apparently dependent on host recognition of tumor specific transplantation antigens in conjunction with tumor cell major histocompatibility complex (MHC) antigens. Recent studies in this laboratory have established that (1)\resistance to the 402AX teratocarcinoma is genetically controlled; (2)\resistance is mediated by lymphoid cells; and (3)\MHC antigen-negative 402AX cells MHC become MHC antigen positive when passaged in genetically resistant host mice. Genetically resistant hosts, therefore, have the ability to regulate tumor cell antigens that are critically important in rejection of the tumor. The goal of this proposal is to understand, at the cellular and molecular levels, how a genetically resistant mouse regulates MHC antigen expression on resident tumor cells. An understanding of host regulation of tumor cell MHC antigens will further our understanding of why certain individuals are susceptible to tumors while other individuals are resistant to tumors. This overall goal will be accomplished by completing the following specific aims: (1)\determine if MHC antigen expression on teratocarcinoma cells is under genetic control, and precisely map the MHC-linked gene responsible for host resistance to the 402AX teratocarcinoma tumor; (2)\biochemically characterize the MHC antigens expressed on in vivo passaged teratocarcinoma cells; (3)\determine the role of beta-2-microglobulin in MHC antigen expression on teratocarcinoma cells; (4)\determine which subpopulation(s) of host lymphoid cells regulates MHC antigen expression on in vivo passaged teratocarcinoma cells; (5)\determine the cellular mechanism(s) of regulation of MHC antigens on teratocarcinoma; (6)\determine precisely which antigens of the MHC are regulated on 402AX teratocarcinoma cells; (7)\determine the molecular level of regulation of MHC antigens on teratocarcinoma cells; and (8)\determine if MHC antigen expression on tumor cells is a function of differentiation of the tumor cells.